title: Modified cisplatin/interferon α-2b/doxorubicin/5-fluorouracil (PIAF) chemotherapy in patients with no hepatitis or cirrhosis is associated with improved response rate, resectability, and survival of initially unresectable hepatocellular carcinoma.
abstract: BACKGROUND
  The purpose of this study was to evaluate the factors associated with response rate, resectability, and survival after cisplatin/interferon α-2b/doxorubicin/5-fluorouracil (PIAF) combination therapy in patients with initially unresectable hepatocellular carcinoma.
  
  
  METHODS
  The study included 2 groups of patients treated with conventional high-dose PIAF (n = 84) between 1994 and 2003 and those without hepatitis or cirrhosis treated with modified PIAF (n = 33) between 2003 and 2012. Tolerance of chemotherapy, best radiographic response, rate of conversion to curative surgery, and overall survival were analyzed and compared between the 2 groups, and multivariate and logistic regression analyses were applied to identify predictors of response and survival.
  
  
  RESULTS
  The modified PIAF group had a higher median number of PIAF cycles (4 versus 2, P = .049), higher objective response rate (36% versus 15%, P = .013), higher rate of conversion to curative surgery (33% versus 10%, P = .004), and longer median overall survival (21.3 versus 10.6 months, P = .002). Multivariate analyses confirmed that positive hepatitis B serology (hazard ratio [HR] = 1.68; 95% confidence interval [CI] = 1.08-2.59) and Eastern Cooperative Oncology Group performance status ≥ 2 (HR = 1.75; 95% CI = 1.04-2.93) were associated with worse survival whereas curative surgical resection after PIAF treatment (HR = 0.15; 95% CI = 0.07-0.35) was associated with improved survival.
  
  
  CONCLUSIONS
  In patients with initially unresectable hepatocellular carcinoma, the modified PIAF regimen in patients with no hepatitis or cirrhosis is associated with improved response, resectability, and survival.
authors.affiliation: Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Ahmed O
authors.initials: AO
authors.lastname: Kaseb
authors.forename: Junichi
authors.initials: J
authors.lastname: Shindoh
authors.forename: Yehuda Z
authors.initials: YZ
authors.lastname: Patt
authors.forename: Robert E
authors.initials: RE
authors.lastname: Roses
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Zimmitti
authors.forename: Richard D
authors.initials: RD
authors.lastname: Lozano
authors.forename: Manal M
authors.initials: MM
authors.lastname: Hassan
authors.forename: Hesham M
authors.initials: HM
authors.lastname: Hassabo
authors.forename: Steven A
authors.initials: SA
authors.lastname: Curley
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Aloia
authors.forename: James L
authors.initials: JL
authors.lastname: Abbruzzese
authors.forename: Jean-Nicolas
authors.initials: JN
authors.lastname: Vauthey
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000601:surgery; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D017322:Clinical Trials, Phase II as Topic; D015331:Cohort Studies; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000009:adverse effects; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000601:surgery; D008875:Middle Aged; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects; D012189:Retrospective Studies; D016019:Survival Analysis; D055815:Young Adult
chemical_list: D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D004317:Doxorubicin; D002945:Cisplatin; D005472:Fluorouracil
keywords: PIAF; chemotherapy; downsizing; hepatocellular carcinoma; liver resection; response; survival; tolerance